Claus Garbe

Basal cell carcinoma : histological classification and body-site distribution

Backgroundu2002 Basal cell carcinoma (BCC) is the most common cancer worldwide in white‐skinned populations. Recent studies suggest that BCC is not a single entity and that different histological subtypes show different clinical behaviour and might have different aetiology.

Time trends of cutaneous melanoma in Queensland, Australia and Central Europe

The objective of this study was to describe recent developments in cutaneous melanoma from the German speaking countries in Europe (Germany, Austria, and Switzerland) and from Queensland, Australia.

Prognostic Factors of Thin Cutaneous Melanoma: An Analysis of the Central Malignant Melanoma Registry of the German Dermatological Society

PURPOSEnThe increasing number of thin cutaneous melanomas (CM) with tumor thickness up to 1 mm demands a detailed analysis of prognostic factors for the classification and grading of these tumors. The aim of the present study was to identify prognostic factors in thin CM.nnnPATIENTS AND METHODSnA series of 12,728 patients with thin incident primary invasive CM and follow-up data recorded between 1976 and 2000 by the German-based Central Malignant Melanoma Registry was analyzed using the multivariate Cox proportional hazard model to evaluate prognostic factors, and classification and regression trees analysis (CART) to define prognostic groups.nnnRESULTSnMultivariate analysis found tumor thickness, sex, age, body site, and histopathologic subtype to be significant prognostic factors of thin CM. Ulceration and regression did not affect prognosis significantly. Prognostic classification based on the results of CART analysis resulted in three groups defined by tumor thickness, age, and sex. Ten-year survival rates of these groups varied between 91.8% and 98.1%, with improved classification as compared with subgroups by tumor thickness alone.nnnCONCLUSIONnClassification by tumor thickness identified prognostic subgroups with highest significance in thin CM, and the classification was improved by the introduction of age and sex. However, neither ulceration nor the level of invasion included in the new American Joint Committee on Cancer TNM system classification, revealed statistical significance as prognostic factors in thin CM.

Functional T Cells Targeting NY-ESO-1 or Melan-A Are Predictive for Survival of Patients With Distant Melanoma Metastasis

PURPOSEnTo analyze the prognostic relevance of circulating T cells responding to NY-ESO-1, Melan-A, MAGE-3, and survivin in patients with melanoma with distant metastasis.nnnPATIENTS AND METHODSnWe examined 84 patients with follow-up after analysis (cohort A), 18 long-term survivors with an extraordinarily favorable course of disease before analysis (> 24 months survival after first occurrence of distant metastases; cohort B), and 14 healthy controls. Circulating antigen-reactive T cells were characterized by intracellular cytokine staining after in vitro stimulation.nnnRESULTSnIn cohort A patients, the presence of T cells responding to peptides from NY-ESO-1, Melan-A, or MAGE-3 and the M category according to the American Joint Committee on Cancer classification were significantly associated with survival. T cells responding to NY-ESO-1 and Melan-A (hazard ratios, 0.29 and 0.18, respectively) remained independent prognostic factors in Cox regression analysis and were superior to the M category in predicting outcome. Median survival of patients possessing T cells responding to NY-ESO-1, Melan-A, or both was 21 months, compared with 6 months for all others. NY-ESO-1-responsive T cells were detected in 70% of cohort A patients surviving > 18 months and in 50% of cohort B patients. Melan-A responses were found in 42% and 47% of patients in cohorts A and B, respectively. In contrast, the proportion was only 22% for NY-ESO-1 and 23% for Melan-A in those who died within 6 months.nnnCONCLUSIONnThe presence of circulating T cells responding to Melan-A or NY-ESO-1 had strong independent prognostic impact on survival in advanced melanoma. Our findings support the therapeutic relevance of Melan-A and NY-ESO-1 as targets for immunotherapy.

Risk factors of incident melanocytic nevi: a longitudinal study in a cohort of 1,232 young German children.

The number of melanocytic nevi is the most important independent risk factor for cutaneous melanoma. Aim of our study was to add information to the controversial discussion on the role of chronic‐moderate and intermittent‐high sun exposure and sunburns for the development of melanocytic nevi by the use of a large longitudinal study. A longitudinal study with a 3‐year follow‐up was conducted in 1,232 young children 2–7 years of age attending 78 public nursery schools in Bochum and Stuttgart, Germany. Total body nevus counts, assessment of pigmentary features and nevus counts on arms of parents were carried out. Parents underwent a standardized interview concerning sun exposure, sunburns and sun‐protective behavior. Applying multiple linear regression analysis higher numbers of incident nevi were associated with host factors like light skin complexion (skin Type II vs. IV, p = 0.022) and freckling of the face (p < 0.001), with parental factors like nevus counts on mothers (p < 0.001) and fathers (p = 0.004) arms and at least one parent being of German descent (p = 0.006), and with environmental factors like intermittent‐high sun exposure during holidays (p < 0.001) and chronic‐moderate ultraviolet radiation at home (p = 0.007). Sunburns were a significant risk factor for nevus development (p = 0.005). Total cumulative sun exposure seems to be the crucial environmental risk factor for the development of nevi, whether the child is exposed to chronic‐moderate or intermittent‐high ultraviolet light doses. Public health education should focus primarily on avoiding sun exposure especially in children with fair skin and parents with high nevus counts.

Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis

Background:Established prognostic factors are of limited value to predict long-term survival and benefit from metastasectomy in advanced melanoma. This study aimed to identify prognostic factors in patients with distant metastasis.Methods:We analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan–Meier survival probabilities and multivariate Cox hazard regression analysis.Results:Serum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses. Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival. Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis. This treatment was associated with favourable survival for patients with normal LDH and S100B values (5-year survival, 37.2%).Conclusion:The serum markers LDH and S100B were both found to be prognostic factors in melanoma patients with distant metastasis. Furthermore, complete metastasectomy had an independent favourable prognostic impact in particular for the patient subgroup with normal LDH and S100B values.

Interventional study in 1,232 young German children to prevent the development of melanocytic nevi failed to change sun exposure and sun protective behavior.

Sunscreens have been proposed as protective measures to inhibit the development of melanocytic nevi in childhood and to decrease the long term risk for cutaneous melanoma development. Our present study investigates the influence of sunscreen use and education on the number of incident melanocytic nevi. A total of 1,812 children in 78 public nursery schools in 2 German cities were randomized to 3 study arms: (i) parents were informed on study purpose and sun protection measures only at an initial educational meeting; (ii) parents received educational material 3 times yearly; and (iii) education and 800 ml free broad spectrum sunscreens with sun protection factor 25 provided on a yearly basis. Final assessment after 3 years follow‐up included 1,232 children (68%). Changes of sun protection habits including sunscreen use were sparse, without any differences attributable to the intervention efforts. As a consequence, there were no significant differences between the 3 study arms for the main outcome measure, the number of incident melanocytic nevi. Analysis of the sunscreen use in the entire cohort irrespective of our study arms did not show any impact on incident nevus numbers in bivariate or multivariate analysis. In conclusion, intervention with educational letters and free sunscreens seemingly had no additional effect on sun‐protection for German children. High prevalence of sunscreen use at study commencement, social desirability, and inadequate application of sunscreens might have partially covered their effect.

Hazard rates for recurrent and secondary cutaneous melanoma: An analysis of 33,384 patients in the German Central Malignant Melanoma Registry

BACKGROUNDnKnowledge about the risk for recurrence and secondary cutaneous melanoma (CM) is an important basis for patient counseling and planning of follow-up examinations.nnnOBJECTIVESnThis study aimed to analyze stage- and time-dependent hazard rates (HR) and discusses current surveillance recommendations.nnnMETHODSnFollow-up data of 33,384 patients with incident CM in stages I to III (American Joint Committee on Cancer 2002) were recorded by the German Central Malignant Melanoma Registry in 1976 through 2007. Survival was based on Kaplan-Meier estimates and HRs were calculated.nnnRESULTSnRecurrences were recorded in 4999 patients (stage I, 7.1%; stage II, 32.8%; and stage III, 51.0%). Ten-year recurrence-free survival was 78.9% (95% confidence interval 73.1-90.5); in stage I, 89.0%; stage II, 56.9%; and stage III, 36.0%. Whereas HR for recurrent CM showed a constantly low level less than or equal to 1:125 per year for stage IA, clearly higher HRs of greater than or equal to 1:40 were recorded in stage IB for the first 3 years and generally in stages II to III. Of all patients 2.3% developed secondary melanomas, with a consistently low HR of less than 1:220 per year.nnnLIMITATIONSnAs German recommendations discontinued regular follow-up examinations after 10 years, no information can be given beyond this time point. Follow-up data of longer than 5 years were available in 41.4% of patients.nnnCONCLUSIONnFor patients at stage IA with thin melanoma and low HR for recurrent CM the need for surveillance remains questionable. For patients with higher HR greater than 1:40 per year, intensified surveillance strategies should be taken into account.

Impact of Ulceration in Stages I to III Cutaneous Melanoma As Staged by the American Joint Committee on Cancer Staging System: An Analysis of the German Central Malignant Melanoma Registry

PURPOSEnIn 2001, the new American Joint Committee on Cancer classification of cutaneous melanoma (CM) introduced ulceration of the primary melanoma as a new key parameter being represented in respective subcategories of the tumor (T) classification. The present study was performed to validate the prognostic significance of ulceration in relation to T thickness and clinical stages of CM (stages I to III).nnnPATIENTS AND METHODSnPatients (N = 15,158) with incident invasive primary nonmetastatic CM and follow-up data recorded between 1976 and 2000 by the German Central Malignant Melanoma Registry were investigated using survival analysis to evaluate prognostic factors such as T thickness, level of invasion, body site, histologic subtype, ulceration, regression, age, and sex.nnnRESULTSnComparisons of survival probabilities according to the Kaplan-Meier method between ulcerated and nonulcerated CM were not statistically significant for subgroups with T thickness < or = 1 mm and more than 4.00 mm (P = .2601 and P = .0699, respectively) but were significant for T thickness of 1.01 to 2.00 mm and 2.01 to 4.00 mm (P < .0001 for both). This result was confirmed in the multivariate analysis. For stage III CM, the impact of ulceration on overall survival was statistically significant in the bivariate Cox model (P = .0111) but not in the multivariate Cox model (P = .0522).nnnCONCLUSIONnWhereas ulceration seems to have a negative impact on the prognosis of patients with stages T2 and T3, a potential influence for patients with stages T1 and T4 could not be established. If factors of the primary CM were to be taken into consideration to judge prognosis of stage III CM, T thickness but not ulceration should be the focus.

Sentinel Lymph Node Dissection in Primary Melanoma Reduces Subsequent Regional Lymph Node Metastasis as Well as Distant Metastasis After Nodal Involvement

BackgroundIn many countries sentinel lymph node dissection (SLND) followed by complete lymphadenectomy if positive is routinely performed treatment for primary cutaneous melanoma. However, the potential survival benefit of SLND is still controversial.MethodsPatients with primary cutaneous melanoma (tumor thickness 1.00xa0mm or greater) diagnosed in the Department of Dermatology, University of Tuebingen, Germany between 1991 and 2000 were included in the study. A total of 439 patients who received SLND were compared retrospectively with 440 patients without SLND with regards to occurring patterns of metastases and disease-free and overall survival. SLND-positive cases and SLND-negative patients with subsequent development of regional lymph node metastasis (SLND-LN+) were compared with non-SLND patients who had developed regional lymph node metastasis (non-SLND-LN+).ResultsRegional lymph node metastases as the first recurrence occurred more frequently in the non-SLND collective (16.5%) compared with the SLND group (7.3%; Pxa0=xa00.001), whereas satellite/in-transit metastases and distant metastases did not differ. Driven by the reduction of regional lymph node metastases, disease-free survival was improved in the SLND collective (Pxa0=xa00.003). No significant difference in overall survival was observed (Pxa0=xa00.090).The risk of dying from melanoma was 2.2 times higher in the non-SLND-LN+ group than in the SLND-LN+ group (Pxa0=xa00.009), while the risk of developing distant metastasis was 2.3 times higher (Pxa0=xa00.002).ConclusionsSLND reduced subsequent regional lymph node metastases and improved disease-free survival, while overall survival remained unaffected. SLND reduced distant metastases and improved overall survival in the subgroups of patients with regional lymph node involvement.